How synapses function in their native environment, during sensation and perception and in the context of network activity, are critical to understanding how they can transmit information and be modified by experience. Traditionally, electrophysiological studies have been carried out under experimental conditions that are profoundly different from the intact brain, where one of the most critical differences is the near absence of background activity in acute brain slices. Thus, the functional connectivity between neurons in active cortical circuits, across different brain states, remains unknown. We propose to investigate the properties of excitatory synapses, not in isolation, but as they function embedded in a dynamic neural network, using both in vitro and in vivo recordings. Analysis will focus on individual synaptic connections between pairs of pyramidal neurons in superficial layers of the rodent somatosensory cortex, a well-characterized exemplar of the mammalian neocortex. Our preliminary data indicates that under conditions of high network activity, excitatory synaptic connections onto multiple neuronal cell types can be effectively silenced by GABAb activation. We will identify the cellular source of GABA responsible for this suppression and examine how GABAb signaling is regulated in vivo. Understanding both the static and dynamic patterns of synaptic connectivity in the neocortex will be essential for understanding circuit function and plasticity in health and disease.